RNA molecules may have survived the hostile conditions of early Earth by clumping together into liquid-like droplets, according to a new study published July 31 in the journal Nature Communications. The research, led by the University at Buffalo, offers a possible answer to one of science's oldest puzzles: how life could have begun before cells existed to protect fragile molecules.
The problem is known as an origins-of-life chicken-or-egg question. RNA molecules need to find each other and interact to do the chemistry that eventually gave rise to DNA, proteins, and the first cells. But without a cell wall to contain them, those molecules would have been scattered and exposed to the harsh temperatures and acidity of the early Earth.
The study found that RNA forms liquid-like droplets, called condensates, when temperatures rise. These membraneless compartments can concentrate RNA molecules, increasing opportunities for them to interact. The researchers found that a tiny chemical difference between RNA and DNA explains why RNA is far better at forming these structures than DNA is. RNA not only forms droplets more readily, but those droplets are also more prone to becoming rigid, gel-like networked structures.
"These findings reveal, for the first time, how remarkably small changes in molecular chemistry can control the emergence of much larger, self-organized biomolecular structures like RNA condensates," says lead corresponding author Priya R. Banerjee, PhD, Twentieth Century Club Professor in the UB Department of Physics.
Banerjee added that the findings could eventually help researchers address deeper questions. "They could allow us to eventually address even deeper questions, like whether these condensates helped bridge the gap between simple molecules and the earliest forms of life," he said.
The study builds on a 2023 paper by Banerjee's group, which first found that RNA tends to organize itself into liquid-like droplets under high temperatures. The current research compared RNA's droplet-forming abilities directly with single-stranded DNA containing essentially the same sequences. The results showed that RNA began forming droplets at temperatures roughly 10 degrees lower than DNA did, pointing to that small but significant chemical distinction between the two molecules.
The work connects to what scientists call RNA world theory, which holds that RNA played a central role in the origin of life on Earth. Because RNA molecules can both carry genetic information and catalyze chemical reactions, they could in theory have performed the chemistry that eventually gave rise to DNA and proteins. The theory has long struggled to explain how unstable RNA could have persisted under harsh prebiotic conditions and how enough RNA could have concentrated in one place to interact before any cells existed. The new research on condensates addresses both problems at once.
The study was done in collaboration with Jerelle Joseph, PhD, assistant professor of chemical and biological engineering at Princeton University. It received support from the National Institutes of Health, the National Science Foundation, and the Hypothesis Fund.
